title: Phytoestrogens and phytoestrogen metabolites differentially modulate immune parameters in human leukocytes.
abstract: Phytoestrogens (PE) including isoflavones and lignans, are a group of substances of plant origin which can act as estrogen agonists or antagonists. While the immunomodulatory effects of isoflavones have been studied, little is known about the impact of lignans and other PE metabolites on the immune system. The aim of the present study was to assess whether PE and their metabolites modulate human leukocyte functions in vitro. We investigated the effects of genistein, daidzein, matairesinol, and secoisolariciresinol, including metabolites such as equol, O-desmethylangolensin, enterodiol, and enterolactone on natural killer cell activity, proliferation, cytokine secretion, as well as apoptotic and necrotic rate of human leukocytes. Genistein, daidzein, and its metabolite equol were the most potent inhibitors of leukocyte functions. Ten micromolars of genistein decreased proliferation, lytic activity of natural killer cells, and cytokine secretions. The latter proved to be the most sensitive marker of immune functions. Lignans and their metabolites had minor effects on the immune system. The antiestrogens Tamoxifen and Fulvestrant did not block the inhibition of cytokine secretion by genistein and equol. In conclusion, while physiological concentrations of isoflavones have minor effects on cytokine secretion, lignans including their major metabolites do not modulate human leukocyte functions in vitro.
authors.affiliation: Max Rubner-Institute, Federal Research Institute for Nutrition and Food, Department of Physiology and Biochemistry of Nutrition, Haid-und-Neu-Strasse 9, 76131 Karlsruhe, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Gredel
authors.forename: Christine
authors.initials: C
authors.lastname: Grad
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rechkemmer
authors.forename: Bernhard
authors.initials: B
authors.lastname: Watzl
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D001711:Biotransformation; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004965:Estrogen Antagonists / Q000494:pharmacology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology*; D008297:Male; D009336:Necrosis / Q000473:pathology; D010587:Phagocytosis / Q000187:drug effects; D048789:Phytoestrogens / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D004965:Estrogen Antagonists; D048789:Phytoestrogens